Viewpoints

Pulse-Chase in the Light Microscope

A recent publication by Gaietta et al. describes the real-time trafficking of connexin, and through the use of different fluors,
researchers can discriminate between “older” and newly synthesized connexins. Goodenough and Postma discuss how the technique
permits the visualization of dynamic building and degradation that occurs in subcellular compartments, and how the method
can be used to analyze protein fates in real time.

Selena E. Bartlett and

Jennifer L. Whistler

The Near-Death Experience of Delta Opioid Receptors Leads to New Drug Targets

Petäjä-Repo et al. have published a recent article describing how ligands for delta opioid receptors can facilitate the maturation
of delta opioid receptors at the endoplasmic reticulum (ER) and promote the surface expression of these receptors. Indeed,
even antagonists of the receptor can promote receptor maturation. Bartlett and Whistler discuss the findings within the article
and how chaperones can rescue immature receptors from proteasome-dependent degradation. Pharmacological interventions can
be designed that target immature ER-bound receptors, and subsequently, facilitate their maturation or degradation to ameliorate
pathological conditions associated with abnormal surface expression of receptors.

Emerging Roles for PKC Isoforms in Immune Cell Function

Two publications by Mecklenbräuker et al. and Miyamoto et al. describe an essential role for protein kinase Cδ (PKCδ) in the
development of immune tolerance, and suggest that PKCδ also participates in mechanisms that prevent autoimmunity. Su, Guo,
and Rawlings discuss these observations within the larger context of determining specific functions for individual isoforms
of PKC in B and T lymphocytes, and the careful control these proteins exert in maintaining proper lymphocyte activation and
tolerance.

Reviews

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Marina E. Wolf

Addiction: Making the Connection Between Behavioral Changes and Neuronal Plasticity in Specific Pathways

Drugs of abuse affect the mechanisms by which the brain processes learning and memory events. Chronically abused substances
wreak havoc with the ability of neurons to undergo normal long-term potentiation (LTP) and long-term depression (LTD), resulting
in maladaptive learning and in the reinforcement of craving and drug-seeking behavior. Changes in neuronal plasticity are
now being successfully mapped to account for drug-related behavioral responses.

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Thomas Tuschl and

Arndt Borkhardt

Small Interfering RNAs: A Revolutionary Tool for the Analysis of Gene Function and Gene Therapy

Like a distant thunderclap growing louder and furiously rolling closer to an observer, the research field that encompasses
RNA silencing (RNA interference or RNAi) has recently exploded with examples of RNAi-mediated regulation in cultured mammalian
cells. Now, RNAi is being exploited to validate protein targets for pharmaceutical intervention, and might prove useful in
correcting genetic abnormalities or metabolically based diseases through gene therapy.

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Roger K. Sunahara and

Ron Taussig

Isoforms of Mammalian Adenylyl Cyclase: Multiplicities of Signaling

Great advances have been made recently in elucidating the structures of adenylyl cyclases (ACs), and in discovering many of
the proteins and small molecules that affect their catalytic activity. Further discovery and refinement of existing observations
will lead to better, more intelligent design of pharmacological therapeutics that can correct abnormal AC activity in disease
states.